Ovejero-Benito María C, Muñoz-Aceituno Ester, Sabador David, Almoguera Berta, Prieto-Pérez Rocío, Hakonarson Hakon, Coto-Segura Pablo, Carretero Gregorio, Reolid Alejandra, Llamas-Velasco Mar, Abad-Santos Francisco, Daudén Esteban
Clinical Pharmacology Department, Hospital Universitario de la Princesa, Instituto Teófilo Hernando, Universidad Autónoma de Madrid (UAM), Instituto de Investigación Sanitaria la Princesa (IIS-IP), Madrid, Spain.
Dermatology Department, Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria La Princesa (IIS-IP), Madrid, Spain.
Exp Dermatol. 2020 Dec;29(12):1225-1232. doi: 10.1111/exd.14215. Epub 2020 Oct 29.
While anti-TNF therapies are effective against psoriasis, 30%-50% of patients do not show an adequate response to these drugs. Different candidate-gene pharmacogenetics studies have identified single nucleotide polymorphisms that may predict anti-TNF drugs response in psoriasis. Nevertheless, only one paper has undertaken a pharmacogenomic approach failing to find significant biomarkers of biological drug response along the whole genome. Furthermore, most of the pharmacogenetic candidate biomarkers identified previously have not been confirmed in a different cohort of patients. The objective of this study was to find biomarkers that could predict anti-TNF drugs response along the whole genome and validate biomarkers identified previously. A genome-wide association study (GWAS) was performed using the Human Omni Express-8 v1.2 Beadchips in 243 psoriasis patients treated with anti-TNF drugs. This study was multicentric and did not interfere with clinical practice. Associations between single nucleotide polymorphisms (SNP) and PASI75 (a 75% reduction with respect to baseline PASI) at 3 months were evaluated. Imputation was performed using SNPs with R > 0.7. There were two SNPs located in NPFFR2 that were close to the significant threshold of 5 × 10 . These data suggest that NPFFR2 might be associated with anti-TNF drug response. However, further studies involving a larger cohort of patients are needed in order to confirm these results.
虽然抗TNF疗法对银屑病有效，但30%-50%的患者对这些药物没有充分反应。不同的候选基因药物遗传学研究已经确定了可能预测银屑病中抗TNF药物反应的单核苷酸多态性。然而，只有一篇论文采用了药物基因组学方法，但未能在全基因组中找到生物药物反应的显著生物标志物。此外，先前确定的大多数药物遗传学候选生物标志物在不同的患者队列中尚未得到证实。本研究的目的是在全基因组中寻找能够预测抗TNF药物反应的生物标志物，并验证先前确定的生物标志物。使用人类全基因组表达8 v1.2芯片对243例接受抗TNF药物治疗的银屑病患者进行了全基因组关联研究（GWAS）。本研究是多中心的，不干扰临床实践。评估了单核苷酸多态性（SNP）与3个月时PASI75（相对于基线PASI降低75%）之间的关联。使用R>0.7的SNP进行插补。在NPFFR2中有两个SNP接近5×10的显著阈值。这些数据表明NPFFR2可能与抗TNF药物反应有关。然而，需要进一步纳入更大患者队列的研究来证实这些结果。
